• Bao Nguyen, Le Luong, Hatam Naase, Marc Vives, Gentjan Jakaj, Jonathan Finch, Joseph Boyle, John W Mulholland, Jong-hwan Kwak, Suhkneung Pyo, Amalia de Luca, Thanos Athanasiou, Gianni Angelini, Jon Anderson, Dorian O Haskard, and Paul C Evans.
• BHF Cardiovascular Sciences Unit, National Heart and Lung Institute, Imperial College London, London, United Kingdom.
• J. Thorac. Cardiovasc. Surg. 2014 Aug 1; 148 (2): 690-697.e3.

ObjectivesSystemic inflammatory responses are a major cause of morbidity and mortality in patients undergoing cardiac surgery with cardiopulmonary bypass. However, the underlying molecular mechanisms for systemic inflammation in response to cardiopulmonary bypass are poorly understood.MethodsA porcine model was established to study the signaling pathways that promote systemic inflammation in response to cardiac surgery with cardiopulmonary bypass under well-controlled experimental conditions. The influence of sulforaphane, an anti-inflammatory compound derived from green vegetables, on inflammation and injury in response to cardiopulmonary bypass was also studied. Intracellular staining and flow cytometry were performed to measure phosphorylation of p38 mitogen-activated protein kinase and the transcription factor nuclear factor-κB in granulocytes and mononuclear cells.ResultsSurgery with cardiopulmonary bypass for 1 to 2 hours enhanced phosphorylation of p38 (2.5-fold) and nuclear factor-κB (1.6-fold) in circulating mononuclear cells. Cardiopulmonary bypass also modified granulocytes by activating nuclear factor-κB (1.6-fold), whereas p38 was not altered. Histologic analyses revealed that cardiopulmonary bypass promoted acute tubular necrosis. Pretreatment of animals with sulforaphane reduced p38 (90% reduction) and nuclear factor-κB (50% reduction) phosphorylation in leukocytes and protected kidneys from injury.ConclusionsSystemic inflammatory responses after cardiopulmonary bypass were associated with activation of p38 and nuclear factor-κB pathways in circulating leukocytes. Inflammatory responses to cardiopulmonary bypass can be reduced by sulforaphane, which reduced leukocyte activation and protected against renal injury.Copyright © 2014 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.

45 keywords...

hide…